Association Between Rapid Progression, Early Mortality, and Imaging in Neonatal-Onset Alexander Disease

Simone Schwarz; Sylke J. Steggerda; Linda S. de Vries; Katharina Schulz; Nikola R. Dürr; Maarten H. Lequin; Thorsten Rosenbaum; Ursula Felderhoff-Müser; Robin-Tobias Jauss; Francisco Brevis Nuñes; Nora Bruns

doi:10.1055/a-2773-9382

Neuropediatrics, Table of Contents

CC BY 4.0 · Neuropediatrics
DOI: 10.1055/a-2773-9382

Original Article

Association Between Rapid Progression, Early Mortality, and Imaging in Neonatal-Onset Alexander Disease

Authors

Simone Schwarz

¹Department of Neonatology and Pediatric Intensive Care Medicine, Sana Clinics Duisburg, Duisburg, Germany

²Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

³TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Sylke J. Steggerda

⁴Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
Linda S. de Vries

⁴Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
Katharina Schulz

⁵Clinic for Radiology and Neuroradiology, Sana Clinics Duisburg, Duisburg, Germany
Nikola R. Dürr

⁵Clinic for Radiology and Neuroradiology, Sana Clinics Duisburg, Duisburg, Germany
Maarten H. Lequin

⁶Department of Radiology, Edward B Singleton, Texas Children's Hospital, Austin, Texas, United States
Thorsten Rosenbaum

⁷Department of Pediatrics, Sana Clinics Duisburg, Duisburg, Germany
Ursula Felderhoff-Müser

²Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

³TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Robin-Tobias Jauss

⁸Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Francisco Brevis Nuñes

¹Department of Neonatology and Pediatric Intensive Care Medicine, Sana Clinics Duisburg, Duisburg, Germany
Nora Bruns

²Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

³TNBS, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Abstract

Alexander disease represents a rare genetic leukodystrophy caused by abnormal astrocytic accumulations of intracytoplasmic proteinaceous inclusions with astrocyte dysfunction. With neonatal onset, survival ranges from 1.5 months to more than 7.5 years, with a possible association between the underlying point mutation, the level of protein accumulation in the cerebral white matter, disease progression, and survival time. We describe the clinical and cerebral imaging features of a female newborn with neonatal-onset Alexander disease caused by a heterozygous de novo point mutation c.1106T > C; p.(Leu369Pro) located in the coil 2B area of the glial fibrillary acidic protein (GFAP). Early-onset seizures, lethargy, and rapid loss of spontaneous movements were accompanied by rapidly evolving brain morphologic abnormalities and early death. The progression of cerebral abnormalities was monitored by magnetic resonance imaging and serial cranial ultrasound exams. As shown in this case study and the accompanying literature review, rapid accumulation of GFAP, as indicated by volume expansion of affected structures on brain imaging, combined with early onset of seizures and rapid clinical deterioration, seems to be associated with poor prognosis. In this case, high-resolution ultrasound offered an easily accessible, serial bedside imaging tool for the detection and follow-up of pathognomonic features of Alexander disease. We observed a close genotype-phenotype interaction in neonatal-onset Alexander disease, with the c.1106T > C; p.(Leu369Pro) mutation in coil2B associated with early death.

Keywords

neonatal leukodystrophy - neonatal onset - Alexander disease - CUS - white matter disease - neonatal seizures

Full Text

References

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